Minimal Gluten Exposure Alters Urinary Volatile Organic Compounds in Stable Coeliac Disease.

Coeliac disease (CD) patients are distinguishable from healthy individuals via urinary volatile organic compounds (VOCs) analysis. We exposed 20 stable CD patients on gluten-free diet (GFDs) to a 14-day, 3 g/day gluten challenge (GCh), and assessed urinary VOC changes. A control cohort of 20 patients continued on GFD. Urine samples from Days 0, 7, 14, 28 and 56 were analysed using Lonestar FAIMS and Markes Gas Chromatography-Time of Flight-Mass Spectrometer (GC-TOF-MS). VOC signatures on D (day) 7-56 were compared with D0. Statistical analysis was performed using R. In GCh patients, FAIMS revealed significant VOC differences for all time points compared to D0. GC-TOF-MS revealed significant changes at D7 and D14 only. In control samples, FAIMS revealed significant differences at D7 only. GC-TOF-MS detected no significant differences. Chemical analysis via GC-MS-TOF revealed 12 chemicals with significantly altered intensities at D7 vs. D0 for GCh patients. The alterations persisted for six chemicals at D14 and one (N-methyltaurine) remained altered after D14. This low-dose, short-duration challenge was well tolerated. FAIMS and GC-TOF-MS detected VOC signature changes in CD patients when undergoing a minimal GCh. These findings suggest urinary VOCs could have a role in monitoring dietary compliance in CD patients.

Breast cancer screening patterns in Jamaican women: review of the largest national mammography clinic.

BACKGROUND: Breast cancer is the leading cause of cancer and cancer related deaths in Jamaican women. In Jamaica, women often present with advanced stages of breast cancer, despite the availability of screening mammography for early detection. The utilization of screening mammography for early breast cancer diagnosis seems to be limited, and this study investigated the national patterns of mammographic screening and the impact of mammography on the diagnosis of breast cancer in Jamaica. METHODS: A retrospective analysis of the records of the largest mammography clinic in Jamaica was done for the period January 2011 to December 2016. Descriptive statistics was performed on relevant patient characteristics with calculation of rates and proportions; cross-tabulations were utilized to assess relationship of covariates being studied on the outcomes of interest. Results are reported in aggregate form with no identifiable patient data. RESULTS: 48,203 mammograms were performed during the study period. 574 women (1.2%) had mammograms suspicious for breast cancer with median age of 57 years (range 30-95 years); 35% were under the age of 50. 4 women with suspicious findings had undergone 'screening mammography', with the remaining having 'diagnostic mammography'. 38% reported previous mammograms, with a mean interval of 8 years between previous normal mammogram and mammogram suspicious for breast cancer. Median age at first screening mammogram was 51 years (range 41-77). CONCLUSION: Breast cancer screening mammography is underutilized in Jamaica. An organized national breast cancer screening programme is recommended to improve adherence to international breast cancer screening guidelines.

Pre-analytical and analytical variables that influence urinary volatile organic compound measurements.

There has been rapidly accelerating interest in the utilization of volatile organic compounds (VOCs) as non-invasive methods for rapid point-of-care medical diagnostics. There is widespread variation in analytical methods and protocols, with little understanding of the effects of sample storage on VOC profiles. This study aimed to determine the effects on VOC profiles of different storage times, at room temperature, prior to freezing, of sealed urine samples from healthy individuals. Analysis using Field Asymmetric Ion Motility Spectrometry (FAIMS) determined the alterations in VOC and total ion count profiles as a result of increasing room temperature storage times. Results indicated that increasing exposure time to room temperature prior to freezing had a threefold effect. Firstly, increased urinary VOC profile variability, with a plateau phase between 12 and 48 hours, before further degradation. Secondly, an increase in total ion count with time exposed to room temperature. Finally, a deterioration in VOCs with each sample run during the analysis process. This provides new insight into the effect of storage of urine samples for VOC analysis using FAIMS technology. Results of this study provide a recommendation for a 12-hour maximum duration at room temperature prior to storage.

2020 update of the WSES guidelines for the management of acute colonic diverticulitis in the emergency setting.

Acute colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of acute left-sided colonic diverticulitis (ALCD) according to the most recent available literature. The update includes recent changes introduced in the management of ALCD. The new update has been further integrated with advances in acute right-sided colonic diverticulitis (ARCD) that is more common than ALCD in select regions of the world.

A multicentre development and validation study of a novel lower gastrointestinal bleeding score-The Birmingham Score.

PURPOSE: Lower gastrointestinal bleeding (LGIB) is common and risk stratification scores can guide clinical decision-making. There is no robust risk stratification tool specific for LGIB, with existing tools not routinely adopted. We aimed to develop and validate a risk stratification tool for LGIB. METHODS: Retrospective review of LGIB admissions to three centres between 2010 and 2018 formed the derivation cohort. Using regressional analysis within a machine learning technique, risk factors for adverse outcomes were identified, forming a simple risk stratification score-The Birmingham Score. Retrospective review of an additional centre, not included in the derivation cohort, was performed to validate the score. RESULTS: Data from 469 patients were included in the derivation cohort and 180 in the validation cohort. Admission haemoglobin OR 1.07(95% CI 1.06-1.08) and male gender OR 2.29(95% CI 1.40-3.77) predicted adverse outcomes in the derivation cohort AUC 0.86(95% CI 0.82-0.90) which outperformed the Blatchford 0.81(95% CI 0.77-0.85), Rockall 0.60(95% CI 0.55-0.65) and AIM65 0.55(0.50-0.60) scores and in the validation cohort AUC 0.80(95% CI 0.73-0.87) which outperformed the Blatchford 0.77(95% CI 0.70-0.85), Rockall 0.67(95% CI 0.59-0.75) and AIM 65 scores 0.61(95% CI 0.53-0.69). The Birmingham Score also performs well at predicting adverse outcomes from diverticular bleeding AUC 0.87 (95% CI 0.75-0.98). A score of 7 predicts a 94% probability of adverse outcome. CONCLUSION: The Birmingham Score represents a simple risk stratification score that can be used promptly on patients admitted with LGIB.

Systematic review with meta-analysis of over 90 000 patients. Does fast-track review diagnose colorectal cancer earlier?

BACKGROUND: National UK data on colorectal cancer (CRC) stage at diagnosis is incomplete. Site-specific fast-track (2-week wait) cancer data are not collected directly by NHS England. Policy making based on these data alone can lead to inaccuracy. AIMS: To review available data on key outcomes (cancer conversion rate and stage at diagnosis) for the UK's lower gastrointestinal 2-week wait pathway. METHODS: A comprehensive literature search was conducted between 2000 and 2017. Primary outcomes were cancer conversion rate and cancer stage at diagnosis. Results were expressed as proportions with 95% CIs. A random effects model was used for meta-analysis; heterogeneity was assessed by I2 . RESULTS: Of 95 papers reviewed, 49 were included in analysis with a total study population of 93,655. Cancer conversion rate was 7.7% (95% CI: 6.9-8.5). The proportion presenting at Dukes A = 11.2% (95% CI 7.4-15.6), B = 36.7% (95% CI 30.8-42.8), C = 35.7% (95% CI: 30.8-40.8) and D = 11.1% (95% CI 7.3-15.5). No colonic pathology was diagnosed in 54.6% (95% CI: 46.2-62.8). CONCLUSIONS: Only 7.7% of patients referred by the 2-week wait pathway were found to have CRC. No beneficial effect on stage at diagnosis was found compared to non-2-week wait referral pathways. Over half of patients had no colonic pathology and detection of adenomas was very low. These results should prompt a reconsideration of the benefits of the 2-week wait pathway in CRC diagnosis and outcomes, with more focus on strategies to improve patient selection.

Time to endoscopy for acute upper gastrointestinal bleeding: Results from a prospective multicentre trainee-led audit.

Background: Endoscopy within 24 h of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24 h of admission). Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between November and December 2017. Analyses were performed to identify factors associated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups. Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2 h (IQR 12.0-35.7), comprising median admission to referral and referral to endoscopy times of 8.1 h (IQR 3.7-18.1) and 6.7 h (IQR 3.0-23.1), respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0-87.5%, p = 0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7:00 and 19:00 hours or via the emergency department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1 d; p = 0.004), but not 30-d mortality (p = 0.344). Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome.

Attitudes to out-of-programme experiences, research and academic training of gastroenterology trainees between 2007 and 2016.

OBJECTIVE: Academic medical training was overhauled in 2005 after the Walport report and Modernising Medical Careers to create a more attractive and transparent training pathway. In 2007 and 2016, national web-based surveys of gastroenterology trainees were undertaken to determine experiences, perceptions of and perceived barriers to out-of-programme research experience (OOP-R). DESIGN SETTING AND PATIENTS: Prospective, national web-based surveys of UK gastroenterology trainees in 2007 and 2016. MAIN OUTCOME MEASURE: Attitudes to OOP-R of two cohorts of gastroenterology trainees. RESULTS: Response rates were lower in 2016 (25.8% vs 56.7%) (p<0.0001), although female trainees' response rates increased (from 28.8% to 37.6%) (p=0.17), along with higher numbers of academic trainees. Over 80% of trainees planned to undertake OOP-R in both surveys, with >50% having already undertaken it. Doctor of Philosophy/medical doctorate remained the most popular OOP-R in both cohorts. Successful fellowship applications increased in 2016, and evidence of gender inequality in 2007 was no longer evident in 2016. In the 2016 cohort, 91.1% (n=144) felt the development of trainee-led research networks was important, with 74.7% (n=118) keen to get involved. CONCLUSIONS: The majority of gastroenterology trainees who responded expressed a desire to undertake OOP-R, and participation rates in OOP-R remain high. Despite smaller absolute numbers responding than in 2007, 2016 trainees achieved higher successful fellowship application rates. Reassuringly more trainees in 2016 felt that OOP-R would be important in the future. Efforts are needed to tackle potential barriers to OOP-R and support trainees to pursue research-active careers.

Oesophageal pemphigoid: a rare cause of dysphagia.

Pemphigus vulgaris (PV) is a rare autoimmune bullous disease which affects the skin and mucous membranes. Oesophageal involvement is rare and has previously been limited to case reports and case series. A recent large case series of 477 PV patients showed that 26/477 (5.4%) had symptomatic oesophageal involvement. We present the case of a 54-year-old Somalian lady with a 10-year history of cutaneous PV, currently in remission, who developed dysphagia and odynophagia and was subsequently found to have oesophageal PV involvement with multiple flaccid bullae which were positive for anti-DSG3 antibodies on in-direct immunofluorescence. She had her treatment switched from azathioprine to mycophenolate and prednisolone, leading to resolution of her symptoms.

Knowledge, awareness, and attitude towards infection prevention and management among surgeons: identifying the surgeon champion.

Despite evidence supporting the effectiveness of best practices of infection prevention and management, many surgeons worldwide fail to implement them. Evidence-based practices tend to be underused in routine practice. Surgeons with knowledge in surgical infections should provide feedback to prescribers and integrate best practices among surgeons and implement changes within their team. Identifying a local opinion leader to serve as a champion within the surgical department may be important. The "surgeon champion" can integrate best clinical practices of infection prevention and management, drive behavior change in their colleagues, and interact with both infection control teams in promoting antimicrobial stewardship.

Multisystem amyloidosis as the unifying diagnosis for constipation, collapse and cardiomyopathy.

Amyloidosis a rare disorder characterised by the deposition of amyloid protein aggregates in different organ systems throughout the body with resulting functional impairment of affected organs. It can present with localised or multisystemic deposits. Diagnosis is often delayed due to the non-specific nature of the symptoms. We present the case of a 59-year-old man with a 12-month history of non-specific symptoms. Investigations revealed Helicobacter pylori positive gastritis. Blood tests showed only a normocytic anaemia and thrombocytopaenia. CT scan showed proximal sigmoid thickening. Biopsies were unremarkable. Echocardiogram and cardiac MRI scan showed restrictive cardiomyopathy. Congo red staining of gastric biopsies showed amyloid deposition. The patient had elevated serum kappa light chains and a bone marrow biopsy confirmed multiple myeloma and he was subsequently diagnosed with systemic light chain (AL) amyloidosis secondary to this. He was started on chemotherapy and parenteral nutrition; however, he deteriorated rapidly and so was started on palliative treatment and discharged home.

An assessment of candidate genes to assist prognosis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is the fourth commonest cancer worldwide, with the second highest mortality rate. Its poor mortality is linked to delayed presentation. There is a drive towards non-invasive biomarker screening and monitoring of many different types of cancer, although with limited success so far. We aimed to determine if any genes from a 32-gene panel could be used to determine GC prognosis. METHODS: We carried out a retrospective study on the expression of 32 genes, selected for their proven or potential links to GC, on historic formalin fixed paraffin-embedded (FFPE) GC specimens from our unit. Gene expression was measured using quantitative nuclease protection assays (qNPA) technology. Following statistical analysis of the results, immunohistochemical staining for eight genes, both discriminating and non-discriminating, was conducted in seven age and sex matched non-metastatic: metastatic GC pairings. The stained samples were reviewed by two blinded consultant histopathologists. RESULTS: Multivariate Cox analysis of the gene expression data revealed metastatic status, age, sex and five genes appeared to influence GC survival. Genes negatively influencing survival included BCAS1, P53 and HSP90AA1 (relative risks 2.20, 3.73 and 7.53 respectively). Genes conveying survival benefit included CASP3 and TERT (relative risks 0.10 and 0.24 respectively). Immunohistochemical staining of seven age and sex matched non-metastatic: metastatic pairs revealed no association between gene expression and protein expression. CONCLUSIONS: Our study found several genes whose expression may affect GC prognosis. However, immunohistochemical analysis revealed no association between gene expression and protein expression. It remains to be determined whether gene expression or protein expression are reliable means of assessing GC prognosis.

Emerging role of thalidomide in the treatment of gastrointestinal bleeding.

Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.

Raising concerns about the Sepsis-3 definitions.

The Global Alliance for Infections in Surgery appreciates the great effort of the task force who derived and validated the Sepsis-3 definitions and considers the new definitions an important step forward in the evolution of our understanding of sepsis. Nevertheless, more than a year after their publication, we have a few concerns regarding the use of the Sepsis-3 definitions.

Domperidone prolongs oral to duodenal transit time in video capsule endoscopy.

PURPOSE: Domperidone is thought to accelerate gastric emptying via D2 receptor antagonism at the gastro-oesophageal and gastro-duodenal junctions. Listed in the BNF as a prokinetic anti-emetic, it has been used in video capsule endoscopy (VCE) to accelerate capsule delivery to the small intestine. We audited VCEs performed at UHCW from 2011, when as standard practice, domperidone was given pre-VCE, to 2012, after its discontinuation due to doubts about its effectiveness. METHODS: Thirty-one patients received oral domperidone 20 mg pre-VCE. Thirty-three patients underwent VCE without domperidone pre-treatment. After 2 h, if the capsule remained intra-gastric, gastroscopy-assisted duodenal delivery was performed. Data was analysed using Mann-Whitney testing. RESULTS: Median oro-duodenal transit was 13 and 30 min in the untreated and domperidone groups, respectively (p = 0.01). Median oro-caecal transit was 242 and 267 min in the untreated and domperidone groups, respectively (p = 0.02). No difference in duodenal-caecal transit was seen (p = 0.60). Six percent of untreated and 13% of domperidone VCEs required gastroscopy-assisted duodenal capsule delivery (p = 0.65). CONCLUSIONS: Unexpectedly domperidone delayed VCE gastric transit. Most studies on domperidone prokinetic effects have been in diabetic gastroparesis, demonstrating that domperidone can achieve good symptomatic relief, but with mixed results for gastric emptying. Our study suggests that any antiemetic effects of domperidone are not mediated through accelerated gastric transit.